Transcriptome study of exendin-4 in the repair of peripheral nerve injury

Objective To investigate the regeneration effect and molecular mechanism of exendin-4 in repairing peripheral nerve injury (PNI), and to provide a new therapeutic pathway and potential therapeutic target for PNI. Methods High-throughput gene chip technology was used to monitor the gene changes of distal sciatic nerve injury in mice before and after exendin-4 treatment, and the differential genes were screened by bioinformatics method. The differential genes were analyzed by gene ontology (GO) enrichment analysis and PPI network analysis to elucidate the molecular mechanism of exendin-4 in repairing PNI nerve regeneration. In addition, we further verified the peripheral nerve repair mechanism of exendin-4 by molecular biology. Results A total of 180 genes with significant expression differences were detected (P<0.05; FC≤0.5 or≥2). Among them, 146 were raised and 34 were lowered. The results of GO analysis focused on histone H4 acetylation, histone acetyltransferase activity, histone acetyltransferase complex, ubiquitin-specific protease activity, ubiquitin hydrolase activity, Ubiquitin-specific protease activity. According to PPI network analysis, the key gene: Matrix metalloproteinase-9 (MMP9) showed the highest Degree of correlation, and exendin-4 had the greatest correlation with PNI repair nerve regeneration. The results of QPCR and Western blot showed that the mRNA and protein expression levels of MMP9 were significantly increased after exendin-4 injection in Schwann cells. Conclusions The results of this study indicate that exendin-4 promotes the proliferation and migration of Schwann cells through MMP9, thereby improving the ability of nerve regeneration. Therefore, our study provides a new insight in repairing peripheral nerve injury.